In vitro studies of human liver microsomal preparations done in our laboratory identify the antifungal agent ketoconazole as a potent inhibitor of cytochrome P450-3A4, the enzyme responsible for biotransformation of the benzodiazepines triazolam and alprazolam in humans. In vitro data predicts a clinically important pharmacokinetic interaction of ketoconazole with triazolam and alprazolam in humans, much as has been reported during concurrent treatment of ketoconazole with terfenadine (seldane). The present study is a controlled evaluation of the potential interaction of ketoconazole with triazolam and with alprazolam, including the clinical consequences of the interaction.